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Get Free AccessAbstract Internalising symptoms in childhood and adolescence are as heritable as adult depression and anxiety, yet little is known of their molecular basis. This genome-wide association meta-analysis of internalising symptoms included repeated observations from 64,641 individuals, aged between 3 and 18. The N-weighted meta-analysis of overall internalising symptoms (INT overall ) detected no genome-wide significant hits and showed low SNP heritability (1.66%, 95% confidence intervals 0.84-2.48%, N effective =132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalising symptoms showing the highest heritability (5.63%, 95% confidence intervals 3.08-8.18%). Additive genetic effects on internalising symptoms appeared stable over age, with overlapping estimates of SNP heritability from early-childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the wellbeing spectrum (| r g |> 0.70), as well as with insomnia, loneliness, attention-deficit hyperactivity disorder, autism, and childhood aggression (range | r g |=0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. The pattern of genetic correlations suggests that childhood and adolescent internalising symptoms share substantial genetic vulnerabilities with adult internalising disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalising symptoms over time and the high comorbidity amongst childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
Eshim S. Jami, Anke R. Hammerschlag, Hill F. Ip, Andrea G. Allegrini, Beben Benyamin, Richard Border, Elizabeth W. Diemer, Chang Jiang, Ville Karhunen, Yi Lu, Qing Lu, Travis T. Mallard, Pashupati P. Mishra, Ilja M. Nolte, Teemu Palviainen, Roseann E. Peterson, Hannah Sallis, Andrey A. Shabalin, Ashley Tate, Elisabeth Thiering, Natàlia Vilor‐Tejedor, Carol A. Wang, Ang Zhou, Daniel E. Adkins, Silvia Alemany, Helga Ask, Qi Chen, Robin P. Corley, Erik A. Ehli, Luke M. Evans, Alexandra Havdahl, Fiona A. Hagenbeek, Christian Hakulinen, Anjali K. Henders, Jouke‐Jan Hottenga, Tellervo Korhonen, Abdullah Al Mamun, Shelby Marrington, Alexander Neumann, Kaili Rimfeld, Fernando Rivadeneira, Judy L. Silberg, Catharina EM van Beijsterveldt, Eero Vuoksimaa, Alyce M. Whipp, Xiaoran Tong, Ole A. Andreassen, Dorret I. Boomsma, Sandra A. Brown, S. Alexandra Burt, William Copeland, E. Jane Costello, Danielle M. Dick, Lindon J. Eaves, K. Paige Harden, Kathleen Mullan Harris, Catharina A. Hartman, Joachim Heinrich, John K. Hewitt, Christian J. Hopfer, Elina Hyppönen, Paul M Ridker, Jaakko Kaprio, Liisa Keltikangas‐Järvinen, Kelly L. Klump, Kenneth Krauter, Ralf Kuja‐Halkola, Henrik Larsson, Terho Lehtimäki, Paul Lichtenstein, Sebastian Lundström, Hermine H. Maes, Per Magnus, Marcus R. Munafò, Jake M. Najman, Pål R. Njølstad, Albertine J. Oldehinkel, Craig E. Pennell, Robert Plomin, Ted Reichborn‐Kjennerud, Chandra A. Reynolds, Richard J. Rose, Andrew Smolen, Harold Snieder, Michael C. Stallings, Marie Standl, Jordi Sunyer, Henning Tiemeier, Sally J. Wadsworth, Tamara L. Wall, Andrew Whitehouse, Gail Williams, Eivind Ystrøm, Michel G. Nivard, Meike Bartels, Christel M. Middeldorp (2020). Genome-wide association meta-analysis of childhood and adolescent internalising symptoms. , DOI: https://doi.org/10.1101/2020.09.11.20175026.
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Type
Preprint
Year
2020
Authors
96
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1101/2020.09.11.20175026
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